Stretch force on vascular smooth muscle cells enhances oxidation of LDL via superoxide production

Inoue, N.; Kawashima, Seinosuke; Hirata, Ken‐ichi; Rikitake, Yoshiyuki; Takeshita, Saori; Yamochi, Wataru; Akita, Hozuka; Yokoyama, Mitsuhiro

doi:10.1152/ajpheart.1998.274.6.h1928

Cited by 33 publications

(32 citation statements)

References 25 publications

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“…Possibly, this was due to an inadequate amount of tissue. Alternatively, the absence of distending pressure may have played a role, since stretch has been found to enhance ROS production in both endothelium and vascular smooth muscle (2,17). In any case, LDCL and EPR spectroscopy in distal pulmonary arteries provided results consistent with the significant increases in DCF fluorescence caused by hypoxia in myocytes from these vessels (Figs.…”

Section: Discussionmentioning

confidence: 67%

Hypoxic constriction and reactive oxygen species in porcine distal pulmonary arteries

Liu

Sham

Shimoda

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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2002.-To determine whether reactive oxygen species (ROS) play an essential role in hypoxic pulmonary vasoconstriction (HPV) and the cellular locus of ROS production and action during HPV, we measured internal diameter (ID) at constant transmural pressure, lucigenin-derived chemiluminescence (LDCL), and electron paramagnetic resonance (EPR) spin adduct spectra in small distal porcine pulmonary arteries, and dichlorofluorescein (DCF) fluorescence in myocytes isolated from these arteries. Hypoxia (4% O 2) decreased ID, increased DCF fluorescence, tended to increase LDCL, and in some preparations produced EPR spectra consistent with hydroxyl and alkyl radicals. Superoxide dismutase (SOD, 150 U/ml) or SOD ϩ catalase (CAT, 200 U/ml) did not alter ID during normoxia but reduced or abolished the constriction induced by hypoxia. SOD also blocked HPV in endotheliumdenuded arteries after restoration of the response by exposure to 10 Ϫ10 M endothelin-1. Confocal fluorescence microscopy demonstrated that labeled SOD and CAT entered pulmonary arterial myocytes. SOD, SOD ϩ CAT, and CAT blocked the increase in DCF fluorescence induced by hypoxia, but SOD ϩ CAT and CAT also caused a stable increase in fluorescence during normoxia, suggesting that CAT diminished efflux of DCF from cells or oxidized the dye directly. We conclude that HPV required increased concentrations of ROS produced by and acting on pulmonary arterial smooth muscle rather than endothelium. vascular smooth muscle; endothelium; electron paramagnetic resonance; dichlorofluorescein; lucigenin; superoxide dismutase; catalase REACTIVE OXYGEN SPECIES (ROS) are thought to play important roles in a wide variety of cellular processes (10,22). In the pulmonary circulation, O 2 -dependent changes in ROS concentrations in pulmonary arterial smooth muscle have been proposed by several laboratories to mediate hypoxic pulmonary vasoconstriction (HPV); however, the details of these hypotheses differ greatly. On one hand, hypoxia is thought to reduce production of ROS by the mitochondrial electron transport chain (METC) (3) or a microsomal NADH oxidase (33, 34). On the other hand, hypoxia is thought to increase production of ROS by the METC (53) or a sarcolemmal NADPH oxidase (13,30,59). Proposals for effector pathways are equally varied and include redox-dependent inactivation of sarcolemmal voltagedependent potassium channels and secondary membrane depolarization (57), NADH-dependent enhancement of cyclic ADP ribose production and secondary activation of ryanodine receptors and calcium release from sarcoplasmic reticulum (60), and H 2 O 2 -and catalase-dependent, nitric oxide-independent activation of soluble guanylate cyclase (33,34).None of these proposals includes endothelial cells, which can be a potent source of ROS and other vasoactive factors (7,29), and are thought to play an essential role in HPV (52). In small distal porcine pulmonary arteries, we found that HPV was 1) similar to HPV in isolated or intact lungs in terms of magnitude, O 2 dependence, temporal charact...

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Section: Discussionmentioning

confidence: 67%

Hypoxic constriction and reactive oxygen species in porcine distal pulmonary arteries

Liu

Sham

Shimoda

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Meyer et al 15 induced luminal pressures on rabbit aorta in vitro and observed that this stretching increased the uptake of LDL into the arterial wall. More recently, Inoue et al 16 observed that mechanical stretching of cultured smooth muscle cells enhances ox-LDL and superoxide production in the exposed cells. 16 Thus, the combination of increased influx of LDL into the arterial wall and increased oxidative stress may offer a mechanistic explanation of how elevated blood pressure enhances the development of atherosclerosis and ox-LDL.…”

Section: Discussionmentioning

confidence: 99%

Increased Arterial Intima-Media Thickness and In Vivo LDL Oxidation in Young Men With Borderline Hypertension

et al. 2000

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Abstract-We used borderline hypertension as a model for prehypertension to examine the early influences of elevated blood pressure on subclinical atherosclerosis, lipoprotein oxidation, and cardiac adaptation. Healthy men (age 37Ϯ4 years) were classified prospectively into 2 groups on the basis of having either borderline hypertension (systolic 130 to 140 mm Hg or diastolic 85 to 89 mm Hg, nϭ16) or normal (Ͻ130/85 mm Hg, nϭ22) blood pressure values during the previous 2 years. The groups were matched for age, body size, and serum cholesterol levels. High-resolution ultrasound was used to measure intima-media thickness (IMT) of the carotid and brachial arteries, cardiac dimensions, and brachial artery endothelial function. Baseline low-density lipoprotein (LDL)-diene conjugation was measured as an estimate of in vivo LDL oxidation (ox-LDL). Compared with normotensive controls, men with borderline hypertension had higher IMT of the carotid artery (0.58Ϯ0.06 versus 0.75Ϯ0.07 mm, PϽ0.001) and IMT of the brachial artery (0.45Ϯ0.05 versus 0.57Ϯ0.07 mm, PϽ0.001), and increased levels of ox-LDL (29Ϯ9 versus 47Ϯ17 mol/L, PϽ0.001), but similar endothelial function. Left ventricular mass was similar in both groups, but there were significant differences in left ventricular geometry. In multivariate analyses, the predictors of carotid IMT were 24-hour systolic blood pressure (PϽ0.001) and ox-LDL (Pϭ0.10). The current study demonstrates evidence of increased subclinical atherosclerosis and ox-LDL in borderline hypertension. These results are consistent with the idea that enhanced ox-LDL may be one of the pathophysiological events related to development of atherosclerosis in men with borderline elevated blood pressure. Key Words: hypertension, borderline Ⅲ oxidized LDL Ⅲ intima-media thickness S everal mechanisms have been suggested to describe how elevated blood pressure might confer the increased risk of coronary artery disease and stroke. These include structural and functional changes in the circulatory system, 1 increased oxidative stress, 2,3 and accelerated atherogenesis. 4 Because hypertension is often associated with other conditions, such as obesity and dyslipidemia, which can also modify vascular structure and function, studies in patients with established hypertension are not ideal in assessing the natural history of vascular and metabolic changes directly associated with blood-pressure elevation. Mildly elevated blood pressure or borderline hypertension (BHT) is a strong risk factor for established hypertension, 5 and this condition offers a useful model for studying prehypertension in humans. The development of noninvasive ultrasound techniques has opened up the field for in vivo studies of arterial structure and function in asymptomatic young subjects. 6 By using BHT as model for prehypertension and studying only healthy young subjects, it is possible to examine the early cardiovascular and metabolic manifestations related to elevated blood pressure levels without the confounding effects mediated by other risk ...

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“…In injured vessels, vascular stretch affects both the endothelium and vascular smooth muscle. Increased production of ROS in response to cyclic mechanical stretch has been described in endothelial cells (6,104,170,171), vascular smooth muscle cells (62,74,113), fibroblasts (8), and cardiac myocytes (4). Superoxide appears to be the initial species generated in these cell types.…”

Section: Cyclic Stretch and Control Of Ros Productionmentioning

confidence: 99%

Cyclic Stretch, Reactive Oxygen Species, and Vascular Remodeling

Birukov

2009

Antioxidants & Redox Signaling

193

155

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Blood vessels respond to changes in mechanical load from circulating blood in the form of shear stress and mechanical strain as the result of heart propulsions by changes in intracellular signaling leading to changes in vascular tone, production of vasoactive molecules, and changes in vascular permeability, gene regulation, and vascular remodeling. In addition to hemodynamic forces, microvasculature in the lung is also exposed to stretch resulting from respiratory cycles during autonomous breathing or mechanical ventilation. Among various cell signaling pathways induced by mechanical forces and reported to date, a role of reactive oxygen species (ROS) produced by vascular cells receives increasing attention. ROS play an essential role in signal transduction and physiologic regulation of vascular function. However, in the settings of chronic hypertension, inflammation, or acute injury, ROS may trigger signaling events that further exacerbate smooth muscle hypercontractility and vascular remodeling associated with hypertension and endothelial barrier dysfunction associated with acute lung injury and pulmonary edema. These conditions are also characterized by altered patterns of mechanical stimulation experienced by vasculature. This review will discuss signaling pathways regulated by ROS and mechanical stretch in the pulmonary and systemic vasculature and will summarize functional interactions between cyclic stretch-and ROS-induced signaling in mechanochemical regulation of vascular structure and function.

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Stretch force on vascular smooth muscle cells enhances oxidation of LDL via superoxide production

Cited by 33 publications

References 25 publications

Hypoxic constriction and reactive oxygen species in porcine distal pulmonary arteries

Hypoxic constriction and reactive oxygen species in porcine distal pulmonary arteries

Increased Arterial Intima-Media Thickness and In Vivo LDL Oxidation in Young Men With Borderline Hypertension

Cyclic Stretch, Reactive Oxygen Species, and Vascular Remodeling

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